Acute Respiratory Distress Syndrome: Innovative Therapies

Greg S. Martin; Gordon R. Bernard

doi:10.1055/s-2001-15786

Seminars in Respiratory and Critical Care Medicine, Inhaltsverzeichnis

Semin Respir Crit Care Med 2001; 22(3): 293-306
DOI: 10.1055/s-2001-15786

Acute Respiratory Distress Syndrome: Innovative Therapies

Greg S. Martin¹ , Gordon R. Bernard²

¹Division of Pulmonary and Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia
²Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University; Medical Intensive Care Unit, Vanderbilt University Medical Center, Nashville, Tennessee

Abstract

ABSTRACT

Since its description in 1967, the acute respiratory distress syndrome (ARDS) has become one of the most studied pathophysiological processes in intensive care units worldwide. The current state of knowledge about this severe illness and its associated mediators has come from the study of relevant animal models. In the mid-1970s, the development of the sheep model of ARDS and later, the porcine model, led to the discovery of a wide variety of inflammatory lipid mediators, cytokines, and proteases, to name but a few. Recognition of the presence of such highly toxic mediators associated with the development of ARDS has led to numerous potential targets for drug development toward therapeutic intervention.

Through implementation of a standardized definition for ARDS and its less severe sibling acute lung injury (ALI), growth in patient-oriented research has been possible. Substantial numbers of new therapies have been brought forth and examined in recent years, many of which remain controversial. This article is a critical appraisal of the potential therapeutic options investigated in recent years for the management of ALI/ARDS.

KEYWORD

ARDS - pathophysiology - sepsis - endotoxin - corticosteroids - cyclo-oxygenase - cytokines - surfactant

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REFERENCES

1 Hellman J, Warren H S. Antiendotoxin strategies. Infect Dis Clin North Am . 1999; 13 371-77
2 Wheeler A, Bernard G. Immunological therapy of endotoxaemia: anti-endotoxin antibodies. In: Landon J, Chard T, eds. Therapeutic Antibodies London: Springer-Verlag 1995: 177
3 Gorelick K, Scannon P, Hannigan J. Randomized placebo controlled study of monoclonal anti-endotoxin antibody. In: Larrick J, Borrebaeck C, eds. Therapeutic Monoclonal Antibodies New York: Stratton 1990: 253
4 Angus D C, Birmingham M C, Balk R A. E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: a randomized controlled trial. JAMA . 2000; 283(13) 1723-1730
5 Ziegler E J, Fisher Jr J C, Sprung C L. Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin: a randomized, double-blind, placebo-controlled trial. N Engl J Med . 1991; 324(7) 429-436
6 McCloskey R V, Straube R C, Sanders C. Treatment of septic shock with human monoclonal antibody HA-1A: a randomized, double-blind, placebo-controlled trial. Ann Intern Med . 1994; 121(1) 1-5
7 Wright S, Ramos R, Tobias P. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS-binding protein. Science . 1990; 249 1431-1433
8 Hailman E, Lichenstein H, Wurfel M. Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14. J Exp Med . 1994; 179 269-277
9 Schumann R, Leong S, Flaggs G. Structure and function of lipopolysaccharide-binding protein. Science . 1990; 249 1429-1431
10 Feingold K, Funk J, Moser A. Role for circulating lipoproteins in protection from endotoxin toxicity. Infect Immunol . 1995; 63 2041-2046
11 Golenbock D, Will J, Raetz C. Lipid X ameliorates pulmonary hypertension and protects sheep from death due to endotoxin. Infect Immunol . 1987; 55 2471-2476
12 Christ W, Asano O, Robidoux A. E5531, a pure endotoxin antagonist of high potency. Science . 1995; 268 80-83
13 Kawata T, Bristol J, Rose J. Anti-endotoxin activity of a novel synthetic lipid A analog. Prog Clin Biol Res . 1995; 392 499-509
14 Carpati C, Astiz M, Rackow E. Monophosphoryl lipid A attenuates the effect of endotoxic shock in pigs. J Lab Clin Med . 1992; 119 346-353
15 Astiz M, Rackow E, Still J. Pretreatment of normal humans with monophosphoryl lipid A induces tolerance to endotoxin: a prospective, double-blind, randomized, controlled trial. Crit Care Med . 1995; 23 9-17
16 Rogy M, Moldawer L, Oldenburg H. Anti-endotoxin therapy in primate bacteremia with HA-1A and BPI. Ann Surg . 1994; 220 77-85
17 Rogy M, Oldenburg H, Calvano S. The role of bactericidal/permeability-increasing protein in the treatment of primate bacteremia and septic shock. J Clin Immunol . 1994; 14 120-133
18 Von der Mohlen M, Kimmings A, Wedel N. Inhibition of endotoxin-induced cytokine release and neutrophil activation in humans by use of recombinant bactericidal/ permeability-increasing protein. J Infect Dis . 1995; 172 144-151
19 Giroir B, Quint P, Baton P. Preliminary evaluation of recombinant amino-terminal fragment of human bactericidal/permeability-increasing protein in children with severe meningococcal sepsis. Lancet . 1997; 350 1439-1443
20 Garcia C, Saladino R, Thompson C. Effect of a recombinant endotoxin-neutralizing protein on endotoxin shock in rabbits. Crit Care Med . 1994; 22 1211-1218
21 Alpert G, Baldwin G, Thompson C. Limulus antilipopolysaccharide factor protects rabbits from meningococcal endotoxin shock. J Infect Dis . 1992; 164 494-500
22 Roth R, Su D, Child A. Limulus antilipopolysaccharide factor prevents mortality late in the course of endotoxemia. J Infect Dis . 1998; 177 388-394
23 Doig G, Martin C, Sibbald W. Polymyxin-dextran antiendotoxin pretreatment in an ovine model of normotensive sepsis. Crit Care Med . 1997; 25 1956-1961
24 Cheadle W, Hanasawa K, Gallinaro R. Endotoxin filtration and immune stimulation improve survival from gram-negative sepsis. Surgery . 1991; 110 785-791
25 Aoki H, Kodama M, Tani T. Treatment of sepsis by extracorporeal elimination of endotoxin using polymyxin B-immobilized fiber. Am J Surg . 1994; 167 412-417
26 Rinaldo J, Christman J. Mechanisms and mediators of the adult respiratory distress syndrome. Clin Chest Med . 1990; 11 621-632
27 Farrukh I, Michael J, Peters S P. The role of cyclo-oxygenase and lipo-oxygenase oxidant-induced lung injury. Am Rev Respir Dis . 1988; 137 1343-1349
28 Montgomery A, Stager M, Carrico C. Causes of mortality in patients with the adult respiratory distress syndrome. Am Rev Respir Dis . 1985; 132 485-489
29 Sprung C, Caralis P, Marcial E. The effects of high-dose corticosteroids in patients with septic shock: a prospective, controlled study. N Engl J Med . 1984; 311 1137-1143
30 Anonymous. Veterans Administration Systems Sepsis Cooperative Study Group. Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. N Engl J Med . 1987; 317 659-665
31 Bone R, Fisher C, Clemmer T. A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Eng J Med . 1987; 317 653-658
32 Luce J, Montgomery A, Marks J. Ineffectiveness of high-dose methylprednisolone in preventing parenchymal lung injury and improving mortality in patients with sepsis. Am Rev Respir Dis . 1988; 138 62-68
33 Bernard G, Luce J, Sprung C. High-dose corticosteroids in patients with the adult respiratory distress syndrome. N Engl J Med . 1987; 317 1565-1570
34 Meduri G, Chinn A, Leeper K. Corticosteroid rescue treatment of progressive fibroproliferation in late ARDS: patterns of response and predictors of outcome. Chest . 1994; 105 1516-1527
35 Braude S, Haslam P, Hughes D. Chronic adult respiratory distress syndrome: a role for corticosteroids?. Crit Care Med . 1992; 20 1187-1189
36 Hooper R, Kearl R. Established ARDS treated with a sustained course of adrenocortical steroids. Chest . 1990; 97 138-143
37 Meduri G, Headley A, Golden E. Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial. JAMA . 1998; 280 159-165
38 Late Steroid Rescue Study (LaSRS). ARDS Network Web site. Available at: http://hedwig.mgh.harvard.edu/ardsnet/ studyindex.html. Accessed March 15, 2001.
39 Kallenbach J, Lewis M, Zaltman M. ``Low-dose'' corticosteroid prophylaxis against fat embolism. J Trauma . 1987; 27 1173-1176
40 Lindeque B, Schoeman H, Dommisse G. Fat embolism and the fat embolism syndrome: a double-blind therapeutic study. J Bone Joint Surgery . 1987; 698 128-131
41 Schonfeld S, Ploysongsang Y, DiLisio R. Fat embolism prophylaxis with corticosteroids: a prospective study in high-risk patients. Ann Intern Med . 1983; 99 438-443
42 Anonymous. The National Institutes of Health-University of California Expert Panel for Corticosteroids as Adjunctive Therapy for Pneumocystis Pneumonia. Consensus statement on the use of corticosteroids as adjunctive therapy for Pneumocystis pneumonia in the acquired immunodeficiency syndrome. N Engl J Med . 1990; 323 1500-1504
43 Brigham K, Bowers R, McKeen C. Methylprednisolone prevention of increased lung vascular permeability following endotoxemia in sheep. J Clin Invest . 1981; 67 1103-1110
44 Steinberg S, Dehring D, Martin D. Amelioration of pulmonary pathophysiology of adult respiratory distress syndrome by sulindac, a cyclo-oxygenase inhibitor. J Trauma . 1987; 27 1323-1331
45 Borg T, Gerdin B, Modig J. Prophylactic and delayed treatment with indomethacin in a porcine model of early adult respiratory distress syndrome induced by endotoxaemia. Acta Anaesthesiol Scand . 1986; 30 47-59
46 Rinaldo J, Pennock B. Effects of ibuprofen on endotoxin-induced alveolitis: biphasic dose response and dissociation between inflammation and hypoxemia. Am J Med Sci . 1986; 291 29-38
47 Gridec A, Sibbald W, Cheung H. Ibuprofen reduces the progression of permeability edema in an animal model of hyperdynamic sepsis. J Appl Physiol . 1988; 65 1024-1032
48 Wheeler A, Hardie W, Bernard G. The role of cyclo-oxygenase products in lung injury induced by tumor necrosis factor in sheep. Am Rev Respir Dis . 1992; 145 632-639
49 Bernard G, Wheeler A, Russell J. The effects of ibuprofen on the physiology and survival of patients with sepsis. N Engl J Med . 1997; 336 912-918
50 Arons M, Wheeler A, Bernard G. Effects of ibuprofen on the physiology and survival of hypothermic sepsis. Crit Care Med . 1999; 27 699-707
51 Eierman D F, Yagami M, Erme S M, Minchey S R, Harmon P A, Janoff A S. Synergistic prevention of endotoxin induced mortality in rats by PGE1 and particles. Adv Prostaglandin Thromboxane Leukot Res . 1995; 23 341-343
52 Holcroft J, Vassar M, Weber C. Prostaglandin E sub 1 and survival in patients with the respiratory distress syndrome: a prospective trial. Ann Surg . 1986; 203 371-378
53 Bone R, Slotman G, Maunder R. Randomized double-blind, multicenter study of prostaglandin E1 in patients with the adult respiratory distress syndrome. Prostaglandin E1 Study Group. Chest . 1989; 96 114-119
54 Abraham E, Park Y, Covington P. Liposomal prostaglandin E1 in acute respiratory distress syndrome: a placebo-controlled, randomized, double-blind, multicenter, clinical trial. Crit Care Med . 1996; 24 10-15
55 Abraham E, Baughman R, Fletcher E. Liposomal prostaglandin E1 (TLC C-53) in acute respiratory distress syndrome: a controlled, randomized, double-blind, multicenter clinical trial. Crit Care Med . 1999; 27 1478-1485
56 Leff J, Bauer J, Kirkman J. Liposome-entrapped PGE1 posttreatment decreases IL-1 alpha-induced neutrophil accumulation and lung leak in rats. J Appl Physiol . 1994; 76 151-157
57 Walmrath D, Schneider T, Pilch J. Aerosolized prostacyclin in adult respiratory distress syndrome. Lancet . 1993; 342 961-962
58 Meyer J, Theilmeyer G, Van Aken H. Inhaled prostaglandin E1 for treatment of acute lung injury in severe multiple organ failure. Anesth Analg . 1998; 86 753-756
59 Frostell C, Blomquvist H, Hendenstierna G. Inhaled nitric oxide selectively reverses human hypoxic pulmonary vasoconstriction without causing systemic vasodilation. Anesthesiology . 1993; 78 427-435
60 Rossaint R, Slama K, Steudel W. Effects of inhaled nitric oxide on right ventricular function in severe acute respiratory distress syndrome. Intensive Care Med . 1995; 21 197-203
61 Freeman B. Free radical chemistry of nitric oxide: looking at the dark side. Chest . 1994 (suppl); 105 (79S-84S)
62 Rossaint R, Falke K, Lopez F. Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med . 1993; 328 399-405
63 Walmrath D, Schneider T, Schermuly R. Direct comparison of inhaled nitric oxide and aerosolized prostacyclin in acute respiratory distress syndrome. Am J Respir Crit Care Med . 1996; 153 991-996
64 Zwissler B, Kemming G, Habler O. Inhaled prostacyclin (PGI₂) versus inhaled nitric oxide in adult respiratory distress syndrome. Crit Care Med . 1996; 154 1671-1677
65 Putensen C, Hormann C, Kleinsasser A. Cardiopulmonary effects of aerosolized Prostaglandin E1 and nitric oxide inhalation in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med . 1998; 157 1743-1747
66 Dellinger R P, Phillip M. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group. Crit Care Med . 1998; 26 15-23
67 Lundin S, Mang H, Smithies M. Inhalation of nitric oxide in acute lung injury: results of a European multicentre study. Intensive Care Med . 1999; 25(9) 911-919
68 Baldwin S, Simon R, Grum C. Oxidant activity in expired breath of patients with adult respiratory distress syndrome. Lancet . 1986; 1 11-14
69 Heffner J, Repine J. Pulmonary strategies of antioxidant defense. Am Rev Respir Dis . 1989; 140 531-554
70 Pacht E, Timerman A, Lykens M. Deficiency of alveolar fluid glutathione in patients with sepsis and the adult respiratory distress syndrome. Chest . 1991; 100 1397-1403
71 Holguin F, Moss M, Brown L AS, Guidot D. Chronic ethanol ingestion impairs alveolar type II cell glutathione homeostasis and function, and predisposes to endotoxin-mediated acute edematous lung injury in rats. J Clin Invest . 1998; 101(4) 761-768
72 Moss M, Bucher B, Moore F A. The role of chronic alcohol abuse in the development of acute respiratory distress syndrome in adults. JAMA . 1996; 275(1) 50-54
73 Bernard G. N-Acetylcysteine in experimental and clinical acute lung injury. Am J Med . 1991; 91(3C)(suppl 0) 54S-59S
74 Bernard G, Wheeler A, Arons M. A trial of antioxidants N-acetylcysteine and procysteine in ARDS. Chest . 1997; 112 164-172
75 Idell S, Kucich U, Fein A. Neutrophil elastase-releasing factors in bronchoalveolar lavage from patients with adult respiratory distress syndrome. Am Rev Respir Dis . 1985; 132 1098-1105
76 Lee C, Fein A, Lippmann M. Elastolytic activity in pulmonary lavage fluid from patients with adult respiratory-distress syndrome. N Engl J Med . 1981; 304 192-196
77 Tenholder M, Rajagopal K, Phillips Y. Urinary desmosine excretion as a marker of lung injury in the adult respiratory distress syndrome. Chest . 1991; 100 1385-1390
78 Murakami K, Okajima K, Uchiba M. Gabexate mesilate, a synthetic protease inhibitor, attenuates endotoxin-induced pulmonary vascular injury by inhibiting tumor necrosis factor production by monocytes. Crit Care Med . 1996; 24 1047-1053
79 Nishina K, Mikawa K, Takao Y. ONO-5046, an elastase inhibitor, attenuates endotoxin-induced acute lung injury in rabbits. Anesth Analg . 1997; 84 1097-1103
80 Carney D, Lutz C, Picone A. Matrix metalloproteinase inhibitor prevents acute lung injury after cardiopulmonary bypass. Circ . 1999; 100 400-406
81 Brigham K, Meyrick B. Endotoxin and lung injury. Am Rev Respir Dis . 1986; 133 913-927
82 Suter P, Suter S, Girardin E. High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after trauma, shock, or sepsis. Am Rev Respir Dis . 1992; 145 1016-1022
83 Casey L, Balk R, Bone R. Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann Intern Med . 1993; 119 771-778
84 Pinsky M, Vincent J, Deviere J. Serum cytokine levels in human septic shock: relation to multiple-system organ failure and mortality. Chest . 1993; 103 565-575
85 Hyers T, Tricomi S, Dettenmeier P. Tumor necrosis factor levels in serum and bronchoalveolar lavage fluid of patients with the adult respiratory distress syndrome. Am Rev Respir Dis . 1991; 144 268-271
86 Fisher Jr J C, Opal S M, Dhainaut J F. Influence of an anti-tumor necrosis factor monoclonal antibody on cytokine levels in patients with sepsis. Crit Care Med . 1993; 21(3) 318-327
87 Natanson C, Hoffman W D, Suffredini A F. Selected treatment strategies for septic shock based on proposed mechanisms of pathogenesis. Ann Int Med . 1994; 120(9) 771-783
88 Fisher Jr C, Slotman G, Opal S. Initial evaluation of human recombinant interleukin-1 receptor antagonist in the treatment of sepsis syndrome: a randomized, open-label, placebo-controlled multicenter trial. The IL-1RA Sepsis Syndrome Study Group. Crit Care Med . 1994; 22 12-21
89 Fisher C J, Dhainaut J, Opal S. Recombinant human interleukin-1 receptor antagonist in the treatment of patients with sepsis syndrome. JAMA . 1994; 271 1836-1843
90 Wheeler A, Dupont W, Edens T. Polyclonal anti-TNF-α Fab cytokines and clinical outcome in human sepsis [abstract]. Chest . 1999 (suppl); 116 (290S)
91 Bernard G, Wheeler A, Naum C. A placebo controlled, randomized trial of IL-10 in acute lung injury (ALI) [abstract]. Chest . 1999 (suppl); 116 (260S)
92 Petty T, Silvers G, Paul G. Abnormalities in lung elastic properties and surfactant function in adult respiratory distress syndrome. Chest . 1979; 75 571-574
93 Gregory T, Longmore W, Moxley M. Surfactant chemical composition and biophysical activity in acute respiratory distress syndrome. J Clin Invest . 1991; 88 1976-1981
94 Anzueto A, Baughman R, Guntupalli K. Aerosolized surfactant in adults with sepsis-induced acute repiratory distress syndrome. Exosurf Acute Respiratory Distress Syndrome Sepsis Study Group. N Engl J Med . 1996; 334 1417-1421
95 Gregory T J, Steinberg K P, Spragg R. Bovine surfactant therapy for patients with acute respiratory distress syndrome. Am J Respir Crit Care Med . 1997; 155(4) 1309-1315
96 Prost J, Desche P, Jardin F. Comparison of the effects of intravenous almitrine and positive end-expiratory pressure on pulmonary gas exchange in adult respiratory distress syndrome. Eur Respir J . 1991; 4 683-687
97 Reyes A, Lopez-Messa J, Alonso P. Almitrine in acute respiratory failure: effects on pulmonary gas exchange and circulation. Chest . 1987; 91 388-393
98 Papazian L, Roch A, Bregeon F. Inhaled nitric oxide and vasoconstrictors in acute respiratory distress syndrome. Am J Respir Crit Care Med . 1999; 160 473-479
99 Montravers P, Fagon J, Gilbert C. Pilot study of cardiopulmonary risk from pentoxifylline in adult respiratory distress syndrome. Chest . 1993; 103 1017-1022
100 Bacher A, Mayer N, Klimscha W. Effects of pentoxifylline on hemodynamics and oxygenation in septic and nonseptic patients. Crit Care Med . 1997; 25 795-800
101 Abraham E. Lisofylline versus placebo for ALI and ARDS [abstract]. Am J Respir Crit Care Med . 2000; 161(3) A379
102 Slotman G, Burchard K, D'Arezzo A. Ketoconazole prevents acute respiratory failure in critically ill surgical patients. J Trauma . 1988; 28 648-654
103 Yu M, Tomasa G. A double-blind, prospective, randomized trial of ketoconazole, a thromboxane synthetase inhibitor, in the prophylaxis of the adult respiratory distress syndrome. Crit Care Med . 1993; 21 1635-1642
104 Anonymous. The ARDS Network. Ketoconazole for early treatment of acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA . 2000; 283(15) 1995-2002
105 Schuster D P. The case for and against fluid restriction and occlusion pressure reduction in adult respiratory distress syndrome. New Horizons . 1993; 1(4) 478-488
106 Simmons R S, Berdine G G, Seidenfeld J J. Fluid balance and the adult respiratory distress syndrome. Am Rev Respir Dis . 1987; 135 924-929
107 Humphrey H, Hall J, Sznajder I, Silverstein M, Wood L. Improved survival in ARDS patients associated with a reduction in pulmonary capillary wedge pressure. Chest . 1990; 97 1176-1180
108 Mitchell J P, Schuller D, Calandrino F S, Schuster D P. Improved outcome based on fluid management in critically ill patients requiring pulmonary artery catheterization. Am Rev Respir Dis . 1992; 145 990-998
109 Martin G S, Mangialardi R J, Wheeler A P, Bernard G R. Albumin and diuretics in ARDS [abstract]. Am J Respir Crit Care Med . 1999; 159(3) A376
110 Gadek J, DeMichele S, Karlstad M. Effect of enteral feeding with eicosapentaenoic acid, γ-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome. Crit Care Med . 1999; 27 1409-1420
111 Galban C, Montejo J C, Mesejo A. An immune-enhancing enteral diet reduces mortality rate and episodes of bacteremia in septic intensive care unit patients. Crit Care Med . 2000; 28(3) 643-648
112 Bidani A, Tzouanakis A E, Cardenas V J, Zwischenberger J B. Permissive hypercapnia in acute respiratory failure. JAMA . 1994; 272(12) 957-962
113 Takeshita K, Suzuki Y, Nishio K. Effects of hypercapnic acidosis on lipopolysaccharide-induced adherence of leukocytes to human pulmonary endothelial cells [abstract]. Chest . 1999 (suppl); 116 (289S)
114 Fourrier F, Chopin C, Goudemand J. Septic shock, multiple organ failure and disseminated intravascular coagulation: compared patterns of antithrombin III, protein C and protein S deficiencies. Chest . 1992; 101 916-921
115 Baudo F, Caimi T M, de Cataldo E. Antithrombin III replacement therapy in patients with sepsis and/or surgical complications: a controlled double-blind randomized multicenter study. Intensive Care Med. 199; 24 336-342
116 Fourrier F, Jourdain M, Tournoys A. Clinical trial results with antithrombin III in sepsis. Crit Care Med . 2000 (suppl 9); 28 (S38-S43)
117 Camerota A J, Creasey A A, Patla V. Delayed treatment with recombinant human tissue factor pathway inhibitor improves survival in rabbits with gram-negative peritonitis. J Infect Dis . 1998; 177 688-676
118 Bernard G R, Vincent J L, Laterre P F. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med . 2001; 344 609-709
119 Anonymous. International Consensus Conferences in Intensive Care Medicine: Ventilator-associated lung injury in ARDS. Am J Respir Crit Care Med . 1999; 160 2118-2124
120 Ranieri V M, Suter P M, Tortorella C. Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA. 1999; 282(1) 54-61
121 Anonymous. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. New Engl J Med . 2000; 342(18) 1301-1308